|Asst Prof Chen Gang||The overall goal of my research group is to employ cutting-edge biophysical techniques to better understand the structures and the physical-chemical properties of RNAs and RNA-ligand complexes to provide deeper insight into and to facilitate precise control of the diverse biological functions involving RNA. We aim to use the fundamental knowledge to fight neurodegenerative diseases, cancers, bacterial and viral infections by designing and discovering novel therapeutic ligands targeting RNA. To approach the challenging goals, we have assembled a multidisciplinary team with expertise ranging from molecular biophysics, structure biology, computation, chemical synthesis, cell biology, to medical healthcare. The research projects of current interests are: (1) characterizing the molecular recognition interactions (e.g., hydrogen bonding and aromatic base stacking) accounting for structure, stability, and dynamics of RNA structural building blocks such as internal loops, hairpins, triplexes, and pseudoknots, (2) probing the complex energy landscapes of RNA folding and assembly with protein, and (3) designing and discovering therapeutic ligands (small molecules, oligonucleotides, peptides, peptide nucleic acid, etc.) targeting RNA. We employ various conventional and cutting-edge biophysical and biochemical techniques including laser optical tweezers, NMR, UV-Vis, fluorescence, SPR, gel electrophoresis, PCR, chemical synthesis of modified oligonucleotides and peptides, in vitro transcription, protein expression, and cell culture assay. The research experience in the laboratory will help the students to grasp fundamental knowledge and experimental skills, to develop learning skills such as rigorous reasoning and innovative thinking, and to be able to ask and answer important questions within and beyond chemical and molecular sciences.
Ru Ying Puah,= Huan Jia, = Manikantha Maraswami,= Desiree-Faye Kaixin Toh,= Rya Ero,= Lixia Yang, Kiran M. Patil, Alan Ann Lerk Ong, Manchugondanahalli S. Krishna, Ruimin Sun, Cailing Tong, Mei Huang, Xin Chen, Teck Peng Loh, Yong-Gui Gao, Ding Xiang Liu,* and Gang Chen,* (2018) Selective Binding to mRNA Duplex Regions by Chemically Modified Peptide Nucleic Acids Stimulates Ribosomal Frameshift. Biochemistry (Invited for a special issue of Future of Biochemistry), In press.
Manikantha Maraswami, Sreekumar Pankajakshan, Gang Chen* and Teck-Peng Loh* (2017) Palladium-Catalyzed Direct C-H trifluoroethylation of aromatic amides, Org Lett, 19, 4223–4226
Hongzhong Chen, Huan Jia, Huijun Phoebe Tham, Qiuyu Qu, Pengyao Xing, Jin Zhao, Soo Zeng Fiona Phua, Gang Chen,* and Yanli Zhao,* (2017) Theranostic Prodrug Vesicles for Imaging Guided Co-Delivery of Camptothecin and siRNA in Synergetic Cancer Therapy, ACS Appl. Mater. Interfaces, 9, 23536–23543
Desiree-Faye Kaixin Toh,= Kiran M. Patil,= and Gang Chen,* (2017) Sequence-specific and selective recognition of double-stranded RNAs over single-stranded RNAs by chemically modified peptide nucleic acids (Invited Methods Article), J Vis Exp, In press, (= These authors contributed equally to this work).
Zhensheng Zhong, Lixia Yang, Haiping Zhang, Jiahao Shi, Jeya Vandana, Do Thuy Uyen Ha Lam, René C. L. Olsthoorn, Lanyuan Lu, and Gang Chen* (2016) Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation, Sci Rep, 6, 39549.
Toh, D.-F.,= Devi, G.,= Patil, K.M., Qu, Q., Maraswami, M., Xiao, Y., Loh, T.-P., Zhao, Y.,* and Chen, G.* (2016) Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine-purine inversion site of an RNA duplex. Nucleic Acids Res, 44, 9071-82
Jiazi Tan, Jia Xin Jessie Ho, Zhensheng Zhong, Shufang Luo, Gang Chen, and Xavier Roca* (2016) Noncanonical registers and base pairs in human 5’ splice-site selection. Nucleic Acids Res, 44, 3980-21